In the following period we will continue investigations of the pathology of the cell in lethal and sublethal injury by DNA-binding (and other) carcinocidal drugs. We propose to determine the conditions affecting protection, chronicity, recovery and rescue from potentially lethal cell injury by carcinocides. Reinitiation of nuclear function after suppression by actinomycin will be studied. Different modalities (serum inhibitor, pH, cytostatic agents) of imposing arrest of cell cycle progression will be studied, and their effects on the susceptibility of cell populations to cytocidal damage by DNA-binding and other carcinocides will be documented in nontransformed and in cancer cell lines. The differential cytostatic and cytotoxic effects of the cytochalasins, in particular, will be compared in normal and derivative transformed cell lines, and the influence of cytochalasins on their susceptibility to potentially lethal and sublethal injury by phase- and by cycle-specific carcinocidal agents will be described. We intend to compare the kinetic effects and cytotoxicity of carcinocidal agents on the same cell types growing as monolayers and histiotypically in capillary fiber culture. We will attempt to induce carcinogenic transformation with the DNA-binding drugs in vitro.